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Impact of ovariectomy on neurotransmitter receptors BDNF/TrkB and endoplasmic reticulum molecular chaperones in rat hypoglossal nucleus

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Abstract

Currently hypoglossal nerve–genioglossus axis is the major research core of OSA pathogenesis. The pathogenesis of OSA incidence changes before and after menopause needs to be clarified further. Little is known about the influences of ovariectomy on hypoglossal motoneurons. In the research, we utilized a rat ovariectomy model to evaluate the expression changes of 5-HT2A and α1-Adrenergic receptors in the hypoglossal nucleus and to explore the involvement of BDNF/TrkB signaling and endoplasmic reticulum molecular chaperones in the hypoglossal nucleus. Results indicated that the expression of 5-HT2A and α1-Adrenergic receptors reduced dramatically in the hypoglossal nucleus of ovariectomized rats. The apoptosis level of hypoglossal motor neurons increased markedly in the OVX groups. The up-regulated expression of BDNF and down-regulated expression of TrkB were found in the OVX groups. Ovarian insufficiency resulted in the activation of UPR and the loss of CANX-CALR cycle. Estrogen replacement could restore these changes partially. Estrogen level influences the expression of neurotransmitter receptors, and regulates BDNF/TrkB signaling compensation and endoplasmic reticulum homeostasis, which might be one of the pathogenesis of menopausal female OSA. The results reveal a new perspective for studying female OSA from the view of hypoglossal nerve and hormonal changes and attempt to propel 17β-estradiol toward a feasible therapy for female OSA.

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Acknowledgements

Zilong Liu and Shanqun Li conceived and designed the experiments. Huan Lu performed the experiments. Huan Lu and Qinhan Wu analyzed the data. Huan Lu and Qinhan Wu have contributed to manuscript preparation. Huan Lu and Qinhan Wu contributed equally to this work and shared the first authorship.

Funding

This work was supported by grants from The National Key Research and Development Program of China (No. 2018YFC1313600) and the National Natural Science Foundation of China (No. 81900086, 81570081, 81770083).

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Author notes

  1. Huan Lu and Qinhan Wu contributed equally.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Huan Lu

  2. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Fenglin Road 180, Xuhui District, Shanghai, 200032, China

    Huan Lu, Qinhan Wu, Zilong Liu & Shanqun Li

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  1. Huan Lu
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Correspondence to Zilong Liu or Shanqun Li.

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All experimental procedures conformed to the guidelines of National Institutes of Health Guide regarding the care and use of animals and were approved by the Medical Experimental Animal Administrative Committee of Shanghai Medical College of Fudan University. All effects were made to minimize animal suffering.

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Lu, H., Wu, Q., Liu, Z. et al. Impact of ovariectomy on neurotransmitter receptors BDNF/TrkB and endoplasmic reticulum molecular chaperones in rat hypoglossal nucleus. Sleep Biol. Rhythms (2024). https://doi.org/10.1007/s41105-024-00520-5

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